The Wilms tumor suppressor gene, WT1, is essential for kidney and urogenital development and loss of WT1 function results in Wilms tumor, a pediatric cancer of the kidney. The objective of this proposal is to improve our understanding of how WT1 functions in these processes. WT1 is capable of binding to DNA and altering gene transcription. Thus, it is likely that the function of WT1 in development and tumorigenesis is mediated by downstream effectors that are regulated at the transcriptional level by WT1. Manipulation of WT1 in a Wilms tumor cell line and gene expression profiling will be used to identify physiologically relevant transcriptional targets of WT1. Potential targets will be characterized by analysis of the interaction of WTI with their promoter sequences and by analysis of their expression patterns during kidney development and in primary Wilms tumors. The proposed studies will enhance our understanding of the function of WT1 as a differentiation factor and tumor suppressor and have the potential to identify other genes and pathways involved in Wilms tumor and neoplasia in general.